Abstract 11648: Residual Diastolic Cross-Bridge and Decreased Expression of Energy Metabolism Genes in Hypertrophied Rat Hearts Induced by Chronic β-Adrenergic Stimulation
Background: Elucidation of the mechanism of diastolic heart failure is important. However, the precise mechanism of incomplete relaxation has been unknown in hypertrophied hearts. The aim of this study is to confirm the existence of residual cross-bridge formation at diastole and abnormal expression of energy metabolism genes in hypertrophied hearts.
Methods and Results: Male Wistar rats (9 weeks old) received a vehicle (control), isoproterenol (ISO) or ISO + β1-blocker metoprolol (MET) subcutaneously (n=5-8 in each group). After 7 days, compared with those in control and ISO+MET groups, ISO administration increased heart weight per body weight (P<0.01), left ventricular (LV) wall thickness (P<0.05), LV end-diastolic pressure (P<0.05) and tau (P<0.05) and decreased e’ (P<0.05). X-ray diffraction analysis showed that reflection intensity ratio (I(1,0)/I(1,1)) at diastole was not different before and after treatment of butanedione monoxime (BDM), which inhibits actin-myosin interaction and induces complete relaxation, in control hearts. However, I(1,0)/I(1,1) was significantly increased after BDM in ISO group (P<0.005, n=14 experiments), showing the existence of residual cross-bridge formation during diastole in the hypertrohied hearts. DNA microarray analysis and real-time PCR of ISO-treated heart showed decreases in expression levels of glucose metabolism genes, glucose transporter GLUT4 and pyruvate dehydrogenase phosphatase isoenzyme1 (PDP1), and alpha-myosin heavy chain (alpha-MHC) gene, which has higher ATPase activity than beta-MHC.
Conclusions: Residual cross-bridge formation at diastole and abnormal expression of energy metabolism genes were found along with incomplete relaxation in hypertrophied hearts.
- © 2011 by American Heart Association, Inc.